Atrial appendage occlusion and arrhythmia treatment

ABSTRACT

Atrial appendage occlusion devices and cardiac monitoring positioned within the left atrial appendage and/or left atrium. In some embodiments the devices include an anchoring portion adapted to anchor the device in place adjacent the left atrial appendage, the anchoring portion comprising distal deformable anchoring portion adapted to be deployed in the left atrial appendage and a proximal deformable anchoring portion being adapted to be deployed in the left atrium, a barrier element secured to the anchoring portion and adapted to cover the left atrial appendage when implanted, and adapted to prevent blood clots from passing through the barrier element, and a cardiac monitoring element secured to at least one of the anchoring portions, the monitoring element including one or more sensors within in the left atrial appendage and/or left atrium and adapted to monitor left atrial cardiac data.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 15/876,128, filed Jan. 12, 2018, which is acontinuation application of U.S. patent application Ser. No. 13/368,685,filed Feb. 8, 2012, which claims priority to U.S. Provisional PatentApplication No. 61/441,627, filed Feb. 10, 2011, the entire disclosureof which is incorporated by reference herein.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

BACKGROUND OF THE DISCLOSURE

Atrial fibrillation (“AF”) is an arrhythmia of the heart that results ina rapid and chaotic heartbeat, producing lower cardiac output andirregular and turbulent blood flow in the vascular system. The leftatrial appendage (“LAA”) is a cavity extending from the lateral wall ofthe left atrium between the mitral valve and the root of the leftpulmonary veins. The LAA normally contracts with the rest of the leftatrium during a normal heart cycle, keeping blood from becoming stagnanttherein, but often fails to contract with any vigor in patientsexperiencing AF due to the discoordinate electrical signals associatedwith AF. The result is that blood tends to pool in the LAA, which canlead to the formation of blood clots therein. The blood clots can thenpropagate out from the LAA into the left atrium. Since blood from theleft atrium and ventricle supply the heart and brain, blood clots fromthe LAA can obstruct blood flow thereto, causing heart attacks, strokes,or other organ ischemia. Blood clots form in the LAA in about 90% ofpatients with atrial thrombus. Patients with AF account for one of everysix stroke patients, and thromboemboli originating from the LAA are thesuspected culprit in the vast majority of these cases. More than 3million Americans have AF, which increases their risk of stroke by afactor of 5. Elimination or containment of thrombus formed within theLAA of patients with AF will significantly reduce the incidence ofstroke in those patients.

Administering an anticoagulant such as warfarin is the most commonlyprescribed treatment for stroke prevention in patients with AF. Theeffectiveness of warfarin, however, is challenged due to serious sideeffects, lack of patient compliance in taking the medication, a narrowtherapeutic window, and an increased risk of bleeding.

LAA occlusion can be used as an alternative for patients who cannot useoral anticoagulants such as warfarin. Approximately 17% of patientscannot take anticoagulants because of a recent or previous bleeding,non-compliance, or pregnancy. Current US FDA-approved occlusion methodsstaple the LAA closed or suture and excise the appendage. Studies,however, have shown these techniques produce inconsistent results. Somenew approaches, currently under FDA investigation, deliver an implantfrom within the vascular system.

Devices are needed, however, to more consistently and effectivelyprevent clots from entering the atrium from the appendage. Whileblocking the appendage from the atrium can prevent thrombus fromentering the atrium, an approach that can also provide therapy for thearrhythmia will reduce the risk of stroke while treating the arrhythmia.

SUMMARY OF THE DISCLOSURE

One aspect of the disclosure is an implantable cardiac orifice occlusiondevice and cardiac monitoring device comprising: an anchoring portionadapted to anchor the device in place adjacent the left atrialappendage, a barrier element secured to the anchoring portion andadapted to cover the left atrial appendage when implanted, and adaptedto prevent blood clots from passing through the barrier element, and acardiac monitoring element secured to the anchoring portion, themonitoring element including one or more sensors positioned within inthe left atrial appendage and/or left atrium adapted to monitor leftatrial cardiac data.

In some embodiments the left atrial cardiac data includes at least onemember of a group consisting of: electrical activity, blood pressure,pulse and ECG data.

In some embodiments the one or more sensors are configured to acquiredata to calculate and/or determine at least one member of a groupconsisting of: AF burden, left atrial pressure, temperature,transthoracic impedance, impending atrial fibrillation and impendingventricular fibrillation.

In some embodiments the monitoring element further comprises circuitryconfigured to process the monitored data.

In some embodiments the monitoring element is configured to monitor dataover time.

In some embodiments the cardiac monitoring element is adapted to storethe data and/or wirelessly transmit the data to an external device.

In some embodiments the cardiac monitoring element may continuouslytransmit the data to the external device and/or receive a signal from anexternal device.

In some embodiments further comprising a treatment element adapted toprovide at least one treatment selected from a group consisting of:treating an arrhythmia, pacing cardiac tissue, and delivering atherapeutic agent.

In some embodiments the treatment element is a drug delivery deviceadapted to deliver a drug or other agent into the left atrium and/orleft atrial appendage.

In some embodiments the anchoring portion, the barrier element, and thecardiac monitoring element are integrated into a singular implantabledevice.

In some embodiments the anchoring portion comprises a distal deformableanchoring portion and a proximal deformable anchoring portion, thedistal anchoring portion adapted to be deployed in a left atrialappendage and anchored to left atrial appendage tissue, wherein theproximal anchoring portion is adapted to be deployed in a left atriumand anchored to left atrial tissue.

One aspect of the disclosure is an implantable cardiac orifice occlusiondevice and cardiac monitoring device positioned within the left atriumand/or left atrial appendage, comprising: an anchoring portion adaptedto anchor the device in place adjacent the left atrial appendage, abarrier element secured to the anchoring portion and adapted to coverthe left atrial appendage when implanted, and adapted to prevent bloodclots from passing through the barrier element, a cardiac monitoringelement secured to the anchoring portion configured to monitor leftatrial cardiac data, the monitoring element comprising one or moresensors within in the left atrial appendage and/or left atrium andadapted to monitor left atrial cardiac data; and circuitry configured toprocess the monitored data, wherein the cardiac monitoring element beingfurther adapted to store the data and/or wirelessly transmit the data toan external device.

In some embodiments the data includes at least one member of a groupconsisting of: electrical activity, blood pressure, pulse and ECG data.

In some embodiments the cardiac monitoring element is further configuredto calculate and/or determine from the acquired the data at least onemember of a group consisting of: AF burden, left atrial pressure,temperature, transthoracic impedance, impending atrial fibrillation andimpending ventricular fibrillation.

In some embodiments the cardiac monitoring element is further adapted toreceive a signal from an external device.

In some embodiments the anchoring portion comprises a distal deformableanchoring portion and a proximal deformable anchoring portion, thedistal anchoring portion adapted to be deployed in a left atrialappendage and anchored to left atrial appendage tissue, wherein theproximal anchoring portion is adapted to be deployed in a left atriumand anchored to left atrial tissue.

One aspect of the disclosure is a method of cardiac orifice blocking andcardiac monitoring using left atrial cardiac data, comprising providingan integrated implantable device comprising an anchoring portion, abarrier element, and a cardiac monitoring element, anchoring theanchoring portion against cardiac tissue near a left atrial appendage toblock the flow of clots through the orifice with the barrier element,positioning one or more sensors of the cardiac monitoring element withinthe left atrial appendage and/or left atrium to monitor left atrialcardiac data, wherein the data includes at least one member of a groupconsisting of: electrical activity, blood pressure, pulse and ECG data.

In some embodiments the method further comprises wirelessly transmittingthe patient data to an external device.

In some embodiments the method further comprises circuitry configured toprocess the monitored patient data, wherein the method furthercomprises.

In some embodiments the method further comprises a treatment elementproviding at least one treatment selected from a group consisting of:treating an arrhythmia, pacing cardiac tissue, and delivering a drug ortherapeutic agent.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary patentable features of the disclosure are set forth in theclaims. A better understanding of the features and advantages of thepresent disclosure will be obtained by reference to the followingdetailed description that sets forth illustrative embodiments, in whichthe principles of the disclosure are utilized, and the accompanyingdrawings of which:

FIG. 1 illustrates an exemplary embodiment of a device adapted toprevent clots from entering the left atrium from the left atrialappendage.

FIG. 2 illustrates an exemplary embodiment of an implant adapted toprevent clots from entering the left atrium from the left atrialappendage.

FIG. 3 illustrates an exemplary embodiment of an implant to preventclots from entering the left atrium from the left atrial appendage.

FIGS. 4A-4E illustrate an exemplary embodiment of an implant adapted toprevent blood flow into the left atrial appendage.

FIG. 5 illustrates an exemplary embodiment of an occlusion implant.

FIG. 6 illustrates a variation on the embodiment in FIG. 5 in which thedevice includes a barrier secured to an expandable anchor.

FIGS. 7A-7C illustrate an exemplary embodiment in which one or more ofthe anchors is made from a tubular element in which portions of the tubeare removed to creates slots therein.

FIGS. 8A and 8B illustrate an exemplary embodiment of an implant thatcan occlude the left atrial appendage.

FIGS. 9A-B illustrate an exemplary embodiment in which the implantcomprises a first anchor and a second anchor that are adapted to clampdown on the tissue at the ostium of the left atrial appendage.

FIG. 10 illustrates an exemplary embodiment of an implant with aratcheting design to secure a portion of the implant in place.

FIG. 11 illustrates an alternative ratcheting embodiment.

FIG. 12 illustrates an implant with arms connected to a distal anchoradapted to monitor and/or treat tissue.

FIGS. 13A-13D illustrate an exemplary embodiment in which the distalappendage anchor has a general conical expanded configuration.

FIGS. 14A-C illustrate an exemplary embodiment of a left atrialappendage occlusion implant.

FIG. 14D illustrates a portion of a left atrium, illustrating therelative positions of left atrial appendage ostium, mitral valve, andleft pulmonary veins ostia.

FIG. 15 illustrates a front view of an exemplary embodiment of anocclusion implant.

FIGS. 16A-C illustrate an exemplary embodiment of an occlusion implant.

FIGS. 17A-B illustrate an exemplary embodiment of an occlusion implant.

FIG. 18 illustrates a side view of an exemplary embodiment of anocclusion implant.

FIGS. 19A and 19B illustrate an exemplary embodiment of an implant.

FIGS. 20A-20C illustrate another exemplary embodiment of an implant.

FIG. 21 illustrates the concept of an implant with a plurality ofoverlapping arms relative to the position of the left atrial appendageopening.

FIG. 22 illustrates an exemplary leaflet with barrier material attachedthereto.

FIG. 23 illustrates an exemplary securing anchor.

FIGS. 24A and 24B illustrate an exemplary embodiment of an implant thatincludes a secondary anchor adapted to be anchored in the distal regionof the left atrial appendage.

FIG. 25 illustrates an exemplary embodiment of an implant.

FIG. 26 illustrates implant with a barrier coupled to a frame.

FIG. 27 illustrates implant which includes a barrier, a frame, aconnector, and a bulb.

FIG. 28 illustrates an alternative embodiment of an implant.

FIG. 29 illustrates a further exemplary embodiment of an implant.

FIG. 30 illustrate an exemplary embodiment in which the implant includesa plurality of expanding arms coupled to a hub.

FIGS. 31A-F illustrate an exemplary method of access to the left atrialappendage and an exemplary implant to be implanted within a patient.

FIG. 32 illustrates an exemplary embodiment in which the implantincludes non-tapering corkscrew.

FIG. 33 illustrates the implant from FIG. 32 in a left atrial appendage.

FIGS. 34A and 34B illustrate an alternative embodiment in which implantis adapted to occlude flow into the left atrial appendage, monitorpatient data, and dispense a therapeutic agent into the left atrialappendage if an arrhythmia is detected.

FIG. 35 illustrates an alternative embodiment of an implant similar tothe implant shown in FIGS. 34A and 34B.

FIGS. 36A and 36B conceptually illustrate a frame element that includesone or more braided elements.

FIGS. 37A-C illustrate an exemplary embodiment of a medical device in anexpanded, or deployed, configuration that is adapted to isolate materialin the left atrial appendage.

DETAILED DESCRIPTION

The disclosure herein relates to isolating clots to prevent them fromentering into an atrium of the heart. While the disclosure focuses onthe left atrial appendage (“LAA”) and the left atrium, the systems canbe used in the right atrial appendage and the right atrium. The devicesmay also be used to close other undesirable orifices in the heart, suchas Atrial Septal Defects (“ASD”) or Patent Foramen Ovales (“PFO”). Theymay also be used in other portions of a body unrelated to the heart. Thedisclosure herein also relates to providing therapy for a detectedcardiac arrhythmia to attempt to prevent the formation of clots withinthe appendage.

One aspect of the disclosure herein relates to LAA occlusion devices andmethods of use. A second aspect of the disclosure herein provides forintra-atrial or intra-LAA cardiac monitoring and therapy for a detectedarrhythmia.

The first aspect can be a stand-alone procedure to occlude the LAA fromthe left atrium. The second aspect can similarly be a stand-aloneprocedure to monitor and provide therapy. Alternatively, the occlusiondevice can be integrated with the therapy aspect. When combined, theocclusion device can be separate and distinct from the monitoring andtherapy components, or they can be combined into an integrated device.

FIG. 1 illustrates an exemplary embodiment of a device adapted toprevent clots from entering the left atrium from the LAA. FIG. 1 shows aperspective view of device 10 in a deployed configuration and positionblocking off fluid communication between a left atrium (“LA”) and a leftatrial appendage (“LAA”). Implant 10 has been deployed adjacent ostium12 to the LAA, engaging a portion of LAA wall 14. Implant 10 includes ananchoring element 16, shown with a generally annular shape. Secured toanchoring element 16, either directly or indirectly, is barrier 18.

Barrier 18 acts as a primary barrier preventing blood from flowing intothe LAA from the LA. Barrier 18 can be any suitable material to preventblood flow into the LAA, such as, for example, expanded PTFE, PTFE,woven polyester fabric, biocompatible materials, polyurethane membrane,etc. In FIG. 1, barrier 18 is secured directly to anchoring element 16,such as by adhesive or stitching with suture material. Barrier 18 can bereinforced by frame 22, which in this embodiment includes a plurality ofelongate elements. The elongate element(s) are secured to anchoringelement 16 and optionally to barrier, extending across the face ofbarrier 18 to reinforce the barrier. The frame can be, for example, oneelongate element extending across the face of barrier 18, while it canalso be a plurality of interconnected elongate elements. Otherconfigurations are within the scope of the disclosure. For example, theframe can be a plurality of braided wires. The frame can be secured tothe distal side of barrier 18, or it can be disposed proximally tobarrier 18.

In alternative embodiments barrier 18 acts as a filter, allowing someblood components to flow into and out of the LAA but preventing clotsfrom flowing from the LAA into the LA. That is, barrier 18 can have aporosity to allow some blood components to flow therethrough whilepreventing clots (or other non-clot blood components) from passingtherethrough. In some embodiments the pores can be from, for example,about 60 microns to about 150 microns in diameter. These pores sizes arenot intended to be limiting.

The anchoring element is adapted to anchor implant 10 in place withinthe LAA. Anchoring element 16 is shown as a generally annularly-shapedcomponent, but can have a variety of shapes. Anchor 16 provides theexpansion force needed to anchor implant 10 in place. The anchor can bemade from a shape memory material such as nitinol, allowing it to bedeformed into a delivery configuration to deliver it to the targetlocation. Upon release from a delivery sheath or catheter, the anchorreverts to its memory configuration. The memory configuration can beadapted to secure the anchor in place based on the outwardly directedforce from the anchor against the tissue. In some embodiments the radialexpansion force is applied by constructing the device from a shapememory material such as, for example, nickel-titanium (nitinol).

FIG. 2 illustrates an exemplary embodiment of an implant adapted toprevent clots from entering the left atrium from the LAA. Implant 30includes anchor 32, frame 38, delivery element 36, and barrier 35.Anchor 32 can be similar to anchor 16 in FIG. 1, and frame 38 can besimilar to frame 22. Implant 30, in addition to barrier 35, includessecondary barrier 34, which is coupled to the distal portion of anchor32, and is disposed further distally than barrier 35. Barrier 34 acts asa secondary barrier to blood flow that prevents blood flow into the LAA.Barrier 34 can be made from any suitable material to occlude the flow ofblood, such as, for example without limitation, PTFE. Delivery element36 is adapted to be releasably coupled to a delivery tool (not shown),allowing implant 30 to be positioned using the delivery tool andreleased therefrom when desired. In alternative embodiments, implant 30need not have barrier 35, and only barrier 34 is included in implant 30to block off the LAA from the left atrium. Additionally, barrier 34 canbe taught relative to anchor 32 such that it does not extend distallyrelative to anchor. In some embodiments barrier 34 and 35 can be madefrom the same material and essentially form a 2-ply barrier.

FIG. 3 illustrates an exemplary embodiment of an implant to preventclots from entering the left atrium from the LAA. Implant 40 includes afirst anchor 46, which can be similar to the anchoring elements shown inFIGS. 1 and 2. Implant 40 also includes anchoring element 44 which isdeployed towards the distal end of LAA 42. Anchoring element 44 iscoupled to anchoring element 46 with struts 48. The struts are coupledto the anchoring elements at a plurality of locations around theannularly-shaped elements. One or more of struts 48 can optionally haveelectrodes 49 disposed thereon, which can be adapted to monitor cardiacactivity and pace cardiac tissue, which is described in more detailherein. Anchor 44 can be biased to expand to a deployed configurationwith a larger diameter than the section of the LAA in which it isdeployed. Anchor 44, as shown, therefore applies an outwardly directedforce on the LAA to help secure it, and the rest of implant 40, inplace.

FIGS. 4A-4E illustrate an exemplary embodiment of an implant adapted toprevent blood flow into the LAA. Implant 50 includes proximal anchor 54,distal anchor 56, and interconnecting therapy elements 58. Anchor 54 isdisposed at the ostium, or just outside the ostium of the LAA. Thelength of therapy elements 58 can be adjusted, but in this embodimentanchor 56 is shown deployed closer to the ostium than to the distal endof the LAA. FIG. 4B illustrates a front view (looking distally) ofdistal anchor 56, wherein anchor 56 is coupled to optional barrier 57.Anchor 56 and barrier 57 can be similar to other anchors and barriersdescribed herein. FIG. 4C illustrates a front view of proximal anchor54, with optional barrier 53. Also shown is delivery element 51 which isadapted to releasably couple to a delivery tool (not shown). Barrier 53does not extend across the delivery element 51. FIG. 4D illustrate aback view (looking proximally) of anchor 54, wherein an optionaladditional barrier layer 59 is secured to anchor 54. FIG. 4E illustratesa perspective view of implant 50 (LAA not shown), illustrating aplurality of therapy elements 58 extending from anchor 54 to anchor 56.Barriers to prevent the flow of blood are also shown.

FIG. 5 illustrates an exemplary embodiment of an occlusion implant.Implant 60 includes a first anchor 62 connected to a second, distal,anchor 64. Distal anchor 64 resembles a traditional stent-like design,and can be made from shape memory material as is known in the art. Theanchors are connected by connectors 66, which can have electrodes 68secured thereto for monitoring and/or pacing as described herein. Distalanchor 64 is expanded in the LAA distal to the ostium to anchor implant60 securely in place, while anchor 62 is expanded closer to the ostium(either just inside or just outside the ostium). Anchor 62 can include abarrier layer as described herein to prevent blood flow into the LAA andto prevent clots from exiting the LAA. FIG. 6 illustrates a variation onthe embodiment in FIG. 5 in which the device includes barrier 72 securedto expandable anchor 78, which is in the form of an expandable latticeof material. The implant also includes anchor 71 secured to anchor 74with connectors 76, which can have electrodes secured thereto (notshown).

FIGS. 7A-7C illustrate an exemplary embodiment in which one or more ofthe anchors is made from a tube in which portions of the tube areremoved to creates slots therein. FIG. 7A illustrates tubular element 80in which material has been removed to form slots 82 therein. By removingmaterial, a plurality of struts are formed extending from the proximalportion to the distal portion. The tube can be cut by, for examplewithout limitation, laser cutting techniques or etching a nitinoltubular element. After the slots are cut in the tubular element, thestruts can be heat set in a desired memory configuration. For example,FIG. 7B illustrates struts 84 (only one shown) in an expandedconfiguration in which a center region expands outwardly to a greaterdiameter than the distal and proximal ends of the struts. The ends ofthe tubes create proximal anchor 86 and distal anchor 88, although thetube can be attached to additional proximal and distal anchors, such asthose described herein. FIG. 7C illustrates an exemplary expandedconfiguration in which struts 84 have a smoother curve than theconfiguration in FIG. 7B. The force of the struts expanding to theirmemory configuration locks the implant in place. While straight cuts areshown in FIG. 7A, a variety of types of cuts can be made in the tubularelement. For example without limitation, helical cuts can be made in thetube. The pattern, width, orientation, etc., of the cuts can be varied,even along the length of the tubular element, to provide for anexpandable configuration with select properties.

FIGS. 8A and 8B illustrate an exemplary embodiment of an implant thatcan occlude the LAA. Implant 90 is a continuous wire form, formed from asingle wire. The wire forms proximal anchor 92, distal anchor 94, andconnects the anchors with sections 96. Implant 90 also includes barrier98 adapted to prevent blood flow into or out of the LAA. Distal anchor94 is secured in the LAA to secure the implant in place, while anchor 92is adapted to expand near the ostium such that barrier 98 blocks theflow of blood into LAA. FIG. 8B illustrates a side view of implant 90.

FIGS. 9A-B illustrate an exemplary embodiment in which the implantcomprises a first anchor and a second anchor that are adapted to clampdown on the tissue at the ostium of the LAA. The two anchors arepositioned on opposite side of the ostium tissue, and once positionedcan revert to a closed configuration, clamping down on the tissue. Theclamping action secures the implant in place and helps provide a sealaround the periphery of the implant. The proximal anchor can include oneor more barrier layers as set forth herein to prevent blood into theLAA. FIG. 9A illustrates implant 100 comprising proximal anchor 102 anddistal anchor 104 connected by elements 106. In their deployedpositions, they are clamped securely around tissue 108 at the ostium ofthe LAA. FIG. 9B illustrates an alternative concept in which thedistance between anchors 101 and 103 can be adjusted by actuation withdelivery device 107. Delivery device 107 can retract actuation element109 proximally, causing teeth 111 to ratchet with respect to proximalanchor 101. Once the tissue at the ostium (not shown) is sufficientlyclamped between the anchors, the delivery device can be released fromactuation element 109. At least one of the anchors can have a barrier,as shown, to prevent the flow of blood into the LAA.

In any of the embodiments above, the proximal anchor (closer to theatrium) can be thin and have a fabric covering on most of the anchor butnot the entire anchor. The uncovered portion of the anchor allows forcardiac monitoring and and/or pacing as described herein. The inner, ordistal, disk can be mostly covered by a fabric.

FIG. 10 illustrates an exemplary embodiment of an implant with aratcheting design to secure a portion of the implant in place. Theimplant includes arms 110 and 112 connected to expandable anchor 118with connector 120. The proximal portions of the arms are positioned tobe engaging the atrium, as shown. The distal portions are positioned tobe inside the LAA, as shown. Once in their respective positions, thearms are actuated towards one another in the direction of the arrowsshown in the figure. This clamps tissue 114 between the arms, securingthe implant in place. The arms can also be adapted with lockingfeatures, such that when engaged they will lock the arms in a lockedconfiguration. Expandable anchor 118 can be of any suitable anchor thatcan be deployed in the LAA and secured against tissue. Once the arms aremoved to their clamped configurations, the blood is blocked from flowinginto the LAA. There may optionally be a barrier layer material securedto the arms, and adapted such that as the arms are closed towards oneanother, the barrier occludes the flow of blood into the LAA.

FIG. 11 illustrates an exemplary embodiment of a portion of implant 130(distal anchor in LAA not shown) includes ratcheting arms similar toFIG. 10. Arms 132 and 134 include tissue piercing elements 138 adaptedto pierce through tissue near the ostium to help more securely anchorarms in place. Implant 130 also includes delivery element 136 which isadapted to releasably couple to a ratcheting mechanism of the deliverysystem to actuate the arms between open and closed positions.

FIG. 12 illustrates implant 140 with arms 142 and 144 connected todistal anchor 148 with connector 146. Distal anchor 148 is adapted to bein contact with LAA tissue as shown to monitor and/or pace tissue asdescribed herein.

FIGS. 13A-13D illustrate an exemplary embodiment in which the distalappendage anchor has a general conical expanded configuration. Thegeneral conical configuration more closely resembles the naturalcontours of the LAA and can more easily be anchored in place within theLAA. Implant 160 includes ratcheting proximal anchor portion 162, asdescribed herein, distal expandable anchor 168, and connector 166. FIG.13B illustrates a side view of a portion of the implant showing theexpandable anchor in a collapsed delivery configuration. FIG. 13C showsan end-view of the same configuration. FIG. 13D shows an end-view of thedistal anchor in an expanded configuration. Distal anchor 164 has ageneral conical shape tapering towards the distal end of the implant.The anchor is made from a single wire secured to connector, but in otherembodiments more than one wire can be used and different configurationsof the anchor can be used.

FIGS. 14A-C illustrate an exemplary embodiment of a LAA occlusionimplant. FIGS. 14A-C illustrate a front view (distally facing), a rearview (proximally facing), and a perspective view, respectively. Implant200 includes a proximal portion 220 (see FIG. 14C) and a distal portion222. Proximal portion 220 includes leaflets, or blades, 202 and 204,each having a generally triangular shape. In some embodiments they havea generally elliptical shape. Once deployed, the leaflets are adapted toengage a portion of the atrial wall. FIG. 14D illustrates a portion of aleft atrium, illustrating the relative positions of LAA ostium 224,mitral valve 226, and left pulmonary veins ostia 228. The mitral valveand ostia to the pulmonary veins are relatively close to the LAA ostium,and as such any implant positioned in the left atrium must not obstructthe flow of blood through the mitral valve or the pulmonary veins.Leaflets 202 are larger than leaflets 204. Leaflets 204 are aligned withthe mitral valve 226 and pulmonary veins ostia 228, respectively, andare sized such that they do not obstruct the flow of blood therethrough.Leaflets 202 are not disposed such that they would block the flow ofblood through the ostia 228 or mitral valve 226 (or any otherstructure), and as such they can be larger than leaflets 204. Ingeneral, any leaflets facing the posterior and superior walls can belonger than leaflets extending towards the mitral valve and pulmonaryveins to provide for more surface contact with the atrial wall.Additionally, the leaflets that extend towards the pulmonary veins canbe slightly curved into the base of the pulmonary veins.

Leaflets 202 each comprise a frame element 201 and a barrier 203.Leaflets 204 are similarly designed. Frame elements 201 have a generaltriangular or elliptical shape, and each has two ends secured to hub212. Frame elements 201 can be, for example, wire made from, forexample, nitinol. Nitinol, or other material with shape memory and/orsuperelastic properties, allows the triangular wire form to be deformedfor loading into a delivery system, with the wire form converting to thetriangular shape upon deployment due to the shape memory and/orsuperelastic properties of the nitinol.

FIGS. 36A and 36B conceptually illustrate a frame element that includesone or more braided elements. In this specific embodiment the frameelement is a braided nitinol wire that is heat set into the deployedconfiguration shown in FIG. 36B. More than one wire can be used as well.The braided pattern allows the frame element to be lengthened into areduced radial dimension for loading, as shown in FIG. 36A. The braidedframe element is adapted to then expand in radial dimension upondeployment from a delivery device through shortening the axial length,as shown in FIG. 36B. The frame element would be secured to a barrier,such as any of the barriers described herein.

Distal portion 222 includes a distal anchor, which in this embodimentcomprises a plurality of anchors 206. Anchors 206 are similar in shapeto the frame elements 201 from leaflets 202 and 204. Anchors 206 can bemade from a wire, and can be made from, for example, nitinol. Eachanchor wire has two ends secured to hub 212, to which leaflets 202 and204 are also secured. The components can be secured to hub 212 with anysuitable technique, such as bonding, welding, etc. Anchors 206 areadapted to expand and anchor in the LAA to secure the implant in place.Any of the distal anchors described herein can be used as the distalportion of implant 200. Also, while three anchors 206 are shown, anysuitable number of anchors can be incorporated into implant 200.Additionally, shapes other than the generally triangular shape can beused. For example, anchors 206 can have four sides rather than three.

Leaflets 202 and 204, and anchors 206 are adapted to be collapsed downinto delivery configurations such that they can be deliveredendoluminally to a target location within the heart. In one exemplaryembodiment, the radially outer portions of leaflets 202 are adapted tocollapse downward and in the proximal direction towards one another suchthat the leaflets are adapted to be disposed within a delivery catheter,sheath, or other delivery instrument. The leaflets can be secured to hubsuch that as they collapse they overlap one another into a staggeredorientation, easing their collapse. A central portion of frame elements201 of each of the leaflets can additionally be adapted to bend outwardto ease in the collapse of frame 201 (shown in phantom on one leaflet inFIG. 14A). Barriers 203 can have slack built into them so that frames101 can collapse. Upon their release from the delivery instrument,leaflets will revert to their memory configuration shown in FIGS. 14A-Cdue to, for example, shape memory properties of frames 101. Similarly,anchors 206 are adapted to collapse into a delivery configuration.Anchors 206 collapse distally and inward towards one another. A centralportion of wires 210 can be adapted to bend along a predeterminedlocation to assist in the collapse of anchors 206 (shown in phantom forone of the anchors 206 in FIG. 14A). As such, when the proximal portionand distal portions of implant are collapsed, the proximal portionextends generally proximally from hub 212, and the distal portionextends generally distally from hub 212. The large leaflets canadditionally optionally act as cardiac monitoring and pacing electrodesas described below. Additionally, the frames of the proximal blades anddistal anchors can have electrodes mounted thereon.

FIG. 15 illustrates a front view of an exemplary embodiment of anocclusion implant. The design is similar to the design in FIGS. 14A-C,and therefore not every feature will be described. Implant 250 includesfour larger blades 252 and two smaller blades 254. There is less spacebetween blades 254 than in the design in FIGS. 14A-C. Blades 254 aresimilarly sized such that they don't interfere with blood flow throughthe pulmonary veins or mitral valve. The distal portion of implant 250comprises a plurality of anchors 256 (six are shown) that are adapted toexpand within the LAA to secure themselves in the LAA. Anchors 256 arestruts extending from tubular element 258. Blades 252 are also securedto tubular element 258.

FIGS. 16A-C illustrate an exemplary embodiment of an occlusion implant.FIG. 16A shows a perspective view, while FIGS. 16B and 16C show side andfront views, respectively. Proximal portion 278 of implant 270 includesfour larger blades 272 and two smaller blades 274 as shown in FIG. 15.Blades 272 and 274 are coupled to tubular hub 282, which has a lumentherethrough. The blades bend, or curve, slightly as they extendradially away from hub 282, which helps them better follow the contourof the atrial wall. Distal portion 280 of implant 270 includes aplurality of distal anchor 276 shown as wire forms extending from hub282. While eight anchors 276 are shown, more or less anchors can beused. Anchors 276 each have two generally straight sections and a curvedsection in between. Anchors 276 extend slightly distally as they extendfrom hub 282.

FIGS. 17A-B illustrate an exemplary embodiment of an occlusion implant.Implant 290 includes relatively larger blades 292 and smaller blades 294secured to hub 298. In the side view of FIG. 17B, it can be seen thatthe blades are axially staggered with respect to the adjacent blade.This can be accomplished by staggering the attachment points of theblades and hubs and the angle at which the blade extends from the hubcan also be varied. Blades 292 and 294 are formed such that they extendfrom the hub initially in the distal direction, and then bend in theproximal direction, forming a curved configuration. The distal portionof implant 290, which is adapted to be anchored in the LAA, includesspokes, or struts 296, each with an anchoring end 299 adapted to eitherpierce the LAA tissue or improve the engagement with the LAA to bettersecure the implant in place.

FIG. 18 illustrates a side view of an exemplary embodiment of anocclusion implant. Implant 310 includes larger leaflets 312 and smallerleaflets 314, similar to other embodiments herein. Leaflets 312 areconfigured such that their radially outer portions extend further in theproximal direction than the radially outer portions of leaflets 314. Theleaflets can be overlapped in an appropriate pattern to create a varyingstructural stiffness or to create a more dense blood barrier. There canbe greater leaflet redundancy in the center region to cover the LAAostium and prevent blood and/or clots to pass through. The configurationof leaflets 312 provides for better engagement with the atrial wall. Theleaflets are secured to hub 316, which has a lumen therethrough. Thedistal anchor includes a plurality of spokes 318, each with an anchoringend as in the embodiment in FIGS. 17A and B.

FIGS. 19A and 19B illustrate an exemplary embodiment of an implant.Implant 330 includes two rows of leaflets, similar to a flower petaldesign. The leaflets are attached to hub 336. A first set of leaflets332 are aligned around hub 336, while leaflets 334 are aligned in asecond row around hub 336. Leaflets 334 are disposed distally relativeto leaflets 332. The distal portion of implant 330 includes spokes 338to be anchored to the LAA tissue. FIG. 19B shows a perspective view ofthe embodiment in the front view of FIG. 19A. In an alternativeembodiment, the leaflets are coupled to the hub around the periphery ofthe hub such that each leaflet is behind, or proximal to, the adjacentleaflet (except for one leaflet). This hub attachment pattern can easein the collapse of the leaflets for delivery.

FIGS. 20A-C illustrate another exemplary embodiment. The leaflets are intwo rows, as can be seen in the side view of FIG. 20C. The front, orproximal, row includes leaflets 354 (five are shown), while back, ordistal, row, includes leaflets 352 (five are shown). From the front viewof FIG. 20A, it can be seen that each leaflet overlaps with the adjacentleaflet. This helps seal off the LAA and prevents blood flow into theLAA. The leaflets and distal anchors 356 are each coupled to hub 360,which has a spherical shape.

In any of the embodiments herein, the leaflet barrier material can beadapted to facilitate cell growth over and within the material. That is,after implantation, cells with grow over and within the barriermaterial, further isolating the LAA from the left atrium. In some of theembodiments, for example in FIGS. 14-20, there are small gaps betweenadjacent leaflets. This can be a way of adapting the device such that itacts like a filter rather than an occlusive barrier. The filter canallow blood to flow into the LAA from the left atrium, but will stillprevent clots from exiting the LAA into the left atrium. FIG. 21illustrates the concept of an implant with a plurality of overlappingarms 382 relative to the position of LAA opening 380. While the leaflets382 cover most of the opening, small gaps can exist that allow blood toflow into the LAA, but are not large enough to allow clots to flow out.The small gaps therefore filter the clots and allow blood to flowthrough. FIG. 22 illustrates an exemplary leaflet 382 with barriermaterial 384 attached thereto. The leaflet also includes securing anchor386 to help secure the leaflet to the atrial wall. FIG. 23 illustratesthe securing anchor 386.

FIGS. 24A and 24B illustrate an exemplary embodiment of an implant thatincludes a secondary anchor adapted to be anchored in the distal regionof the LAA. Implant 400 includes a proximal portion including leaflets402 adapted to engage atrial tissue. Implant 400 also includes anchorelements 404 extending distally from hub 412. Leaflets 402 and anchoringelements 404 each have two generally straight portions connected by acurved portion. The anchoring element may be covered with a barrier, aspreviously sited, and may be pleated or ribbed to conform easily tovarious frame dimensions throughout the procedure. Adding a barrier tothe anchor elements provides a redundancy, essentially two seal barriersto the LAA closure device. There are gaps between leaflets 402 allowingblood to flow therethrough but preventing clots from leaving the LAA.Implant 400 also includes a plurality of struts 408 extending from hub412 to hub 414. Struts 408 can be formed by creating slots in a tubularelement, leaving hubs 412 and 414 at the ends of the tubular element.The struts 408 can be biased in the configuration shown in FIGS. 24A-B.That is, that is their memory configuration that they can revert to ifradially collapsed during delivery. This is similar to the concept shownin FIGS. 7A-7C. Hubs 412 and 414 define a lumen therein, through whichelongate element 410 is disposed. Elongate element 410 has a lumentherein that can be accessed to deliver a variety of devices and/orsubstances into the LAA through elongate element 410. In FIGS. 24A andB, implant 400 also includes expandable bulb anchor 406, which is amaterial that is adapted to be inflated with an inflation fluid (liquidor gas). Upon inflation, it creates an interference fit with the LAAtissue, further assisting in the anchorage of the implant within theLAA. In some embodiments the bulb 406 is a Yulex-type material or othersuitable material with a relatively large expansion ratio. In someembodiments the bulb has a memory configuration to which it is adaptedto revert. The bulb would therefore expand and lock in place within theLAA.

In some embodiments the bulb includes cardiac monitoring and/or pacingcapabilities described in more detail below. For example, the bulb canhave sensing and/or stimulating electrodes incorporated therein or onthe surface adapted to be in contact with LAA tissue. For example, bulb406 can optionally include ring electrode 416 on the surface to be incontact with LAA tissue.

In an alternative embodiment to that shown in FIGS. 24A-B, the implantdoes not include a bulb, but rather a substance can be delivered intothe LAA through elongate member 410, and out the distal end of hub 414.This concept is described in more detail herein.

FIG. 25 illustrates an exemplary embodiment. Implant 420 include barrier422 adapted to prevent blood from entering the LAA (or at leastpreventing clots from leaving the LAA). Barrier 422 is reinforced byframe 424, which includes a plurality of reinforcing elements. Frame 424is coupled to hub 426, from which struts 428 extend to hub 430. Thestruts and hubs can be formed as described herein or in any othersuitable manner. FIG. 26 illustrates implant 440, with barrier 444coupled to frame 442. Frame 442 is secured to hub 446, from which struts450 extend to hub 448. Elongate element 452 and bulb 454 can be similarto their equivalents described in FIGS. 24A and 24B.

FIG. 27 illustrates implant 460, which includes barrier 462, frame 464,connector 466, and bulb 470. Connector 466 is a coil spring, which addsflexibility to the implant. Bulb is coupled to connector 466.

In some embodiments, once the anchors are secured around the LAA ostiumand any other anchors are secured within the LAA, a procedure to verifythe LAA is sealed from the left atrium can be performed. For example, inthe embodiment shown in FIGS. 24A and 24B, once the bulb is expanded,dye can be injected through a lumen in the delivery device (e.g., adelivery catheter), through elongate element 410, and out a distal portin bulb 406. The LAA is sealed off from the atrium if, underfluoroscopy, it is determined that no injection contrast escapes theLAA.

In some embodiments, once a barrier is established between the leftatrium and the LAA, a casting is injected through the distal port of theimplant into the LAA. For example, the casting can be an electricallyconductive casting or a soft polymer casting. In one particular example,ethylene vinyl alcohol (“EVOH”) is injected with a conductive filler ora conductive polymer. The delivery catheter remains in place until thecasting material has solidified and it cannot enter into thebloodstream.

As an alternative to a casting material, in some embodiments asclerosant material is injected through the implant into the LAA. Thesclerosant causes the LAA to shrink. The delivery catheter remains inplace until the sclerosant is no longer active and cannot get into theblood stream.

FIG. 28 illustrates an alternative embodiment. Implant 480 includesostium anchor 482 and LAA anchor 484. Anchor 482 includes barrier 488that blocks the LAA from the atrium. Anchor 486 has a generally helicaldesign. Anchor material 486 can be, for example without limitation, awire, a ribbon material, and can be heat set to expand to an expandedconfiguration to anchor it within the LAA. In some embodiments anchormaterial 486 is a ribbon material coated with a hydrogel to enhance thetissue/anchor adherence. Optionally, a clotting agent is added to thehydrogel material. Optionally, cardiac diagnostic or monitoringcomponents are located in anchor 482 to increase the electricalconduction between the monitoring component and the atrial wall.

FIG. 29 illustrates a further exemplary embodiment. The implant includeshydrogel capsule 502, secured in place within the LAA via struts or arms504 and 508. The implant also includes diagnostic component 506. Arms508 help anchor the implant in place and also connect diagnosticcomponent 506 to atrial tissue. Diagnostic component 506 can monitorcardiac signals via arms 508, and can store date therein or canautomatically transmit that date to an external device without storingit. The cardiac data can be accessed wirelessly using MEMS, or in someembodiments there can be direct access to diagnostic component 506during a catheterization procedure. Capsule 505 can be filled with ahydrogel, or for example, a hydrogel/cyanoacrylate combination or othermedical grade adhesives. Diagnostic component 506 can be adapted forlong-term monitoring (e.g, weeks, months, or years). Subjects in whichthe implant can be implanted may suffer from atrial fibrillation.Diagnostic component 506 allows a physician to continuously monitorcardiac data to detect atrial fibrillation to prevent the patient fromsuffering a stroke. The diagnostic component can additional be adaptedto communicate with an external device. The diagnostic component cancontinuously transmit patient information, such as cardiac electricalactivity, to the external device. The external device could be worn bythe patient or could be a physician's computer. The external device can,based on the patient data, detect atrial fibrillation. The externaldevice can be adapted to transmit a signal to diagnostic component, withinstructions to administer a therapy to the patient to attempt todisrupt the cardiac arrhythmia. In some embodiments the diagnosticcomponent is adapted to detect the occurrence of atrial fibrillation andinitial a therapy to disrupt the cardiac arrhythmia. Diagnosticcomponent 506 can additionally be adapted to monitor other patientinformation, such as blood pressure, etc. Exemplary details of thecardiac monitoring and therapy are provided below.

FIG. 30 illustrate an exemplary embodiment in which implant 530 includesa plurality of expanding arms 532 coupled to hub 533. At the end of eachof the arms is mechanical lock 534. Coiled wire 536 is coupled to hub533 and extends in the proximal direction from hub 533. Arms 532 areadapted to expand and engage LAA tissue to lock the implant in the LAA.Coiled element 536 is adapted to engage tissue surrounding the LAAostium and is adapted to monitor cardiac electrical activity andoptionally pace the tissue to disrupt atrial fibrillation and preventstroke. In some embodiments the implant relies on MEMS for thediagnostic components and optional wireless communication. Implant 530can be adapted to incorporate any features disclosed herein, such asbeing adapted to deliver a casting material into the LAA to form a plugfilling the LAA space.

FIGS. 31A-F illustrates an exemplary method of access to the LAA and anexemplary implant to be implanted within a subject. In FIG. 31A,delivery sheath 552, implant sheath 556, and guidewire 554 gained accessto the LAA via a femoral vein, inferior vena cava, right atrium, fossaovalis, and left atrium approach, an approach known in the art. The LAAcan be accessed via other routes as well. Additionally, the implant canbe positioned surgically. Other minimally invasive approaches can beused. In FIG. 31B, guidewire 554 is extended into the LAA as shown.Steerable delivery sheath 552 and implant sheath 556 are tracked overguidewire 554 into the LAA into the position shown in FIG. 31B. Once thedistal end of the steerable sheath 552 is within the LAA, implant sheath556 is then exposed. As shown in FIG. 31C, corkscrew drive 558 isrotated causing the corkscrew portion 562 of the implant to be deployedfrom the distal end of the implant sheath 556. The corkscrew has atapered configuration. As the corkscrew is advanced, plug 564 is exposedand the rotation of corkscrew 562 penetrates the LAA tissue, whileapplying very little tensile or compressive forces on the LAA. Plug 564is made of a sponge-type material adapted to expand in diameter in thepresence of blood. FIG. 31D shows the corkscrew 562 fullydeployed/rotated and the LAA tissue tapered down the corkscrew until itis “pinched” between the corkscrew and the ID plug. In FIG. 31E, oncethe LAA tissue is securely grasped by the implant, the entire system isretracted proximally. This actuation causes the LAA to collapse andcompress. The corkscrew and plug provide a grasping mechanism whichsupports the weak LAA tissue to prevent tearing during collapse andcompression. The final step in the method is to deploy anchoring barrier570 in the left atrium against the atrial wall, as shown in FIG. 31F.Note that the sequence of deployment is easily altered to deploy 570first, therefore sealing the entrance to the LAA from the atrialpressure and then affixing the corkscrew to the distal area of the LAA.This would potentially address safety concerns of the corkscrew causingthe LAA to leak. The barrier maintains a constant tension on thecollapsed/compressed LAA. The barrier, as shown, is a braided nitinolmaterial with a liner made from, for example, ePTFE. Other barriermaterial and designs can be used. The liner blocks blood flow into theLAA. The corkscrew drive is the released from the proximal portion ofthe implant, leaving the implant within the patient.

FIG. 32 illustrates an exemplary embodiment in which the implantincludes corkscrew 572 that is not tapered as in the embodiment in FIGS.31. At the distal end of corkscrew is bulb 578 that can prevent damageto LAA tissue. The implant also includes plug 574 and proximal anchoringportion 576, comprising a braided material, such as nitinol, and barrier578 adapted to block blood flow into the LAA. FIG. 33 illustrates theimplant from FIG. 32 in a LAA.

The systems herein can also include a cardiac monitoring component tomonitor one or more patient parameters. In some embodiments the systemsinclude a monitoring component adapted to monitor electrical activity ofthe heart over time. The electrical activity of the heart can bemonitored to detect arrhythmias, such as atrial fibrillation. In someembodiments the systems herein are adapted to provide a therapy to treatthe detected arrhythmia. For example, if an arrhythmia is detected, thesystem can be adapted to pace cardiac tissue through electricalstimulation thereof Alternatively, or in addition to, the systems can beadapted to deliver a therapeutic compound to the patient in the event anarrhythmia is detected. The monitoring and/or therapy components of thesystems can optionally be a stand-alone device and not integrated into aLAA occlusion device.

In some embodiments the system includes a monitoring component thatmonitors, or senses, cardiac electrical activity. The sensing componentscan be positioned within the LAA and/or the left atrium, and are adaptedto be in contact with cardiac tissue to sense the electrical activity.The system can monitor ECG data from the patient. In some embodimentsthe sensing component is an electrode or an array of electrodes incontact with cardiac tissue to monitor electrical activity of the heart.

The system is adapted to process the electrical activity data and detectatrial fibrillation from the monitored data. For example, the system canmonitor ECG data and detect AF by, for example, the absence of P waves,with unorganized electrical activity in their place. Irregular R-Rintervals due to irregular conduction of impulses to the ventricles canalso be an indication of atrial fibrillation. The system can includesoftware adapted to automatically detect the occurrence of AF. Thesystem can also be adapted such that electrical activity data istransmitted to health care professionals whose interpretation of theelectrical activity data can supplement or replace the automateddetection process.

The detection component can be integrated with the monitoring componentssuch that it is within the heart. Alternatively the processing componentcan be disposed outside the heart, and optionally external to thepatient. If outside the heart, the processing component can be securedto, for example, the epicardium, or it could be a device that is worn bythe patient close to the heart and that is in wireless communicationwith the intra-cardiac device.

In some embodiments the processing components are disposed within theheart and part of the monitoring device. The intra-cardiac system canthen monitor and detect atrial fibrillation from a device implantedcompletely within the LAA and/or the left atrium.

In some embodiments the processing components of the system are disposedin a device external to the heart such that monitored patient data istransmitted, wirelessly or wired, to the processing component. If AF isdetected therapy will likely be administered as soon as possible, andthus the monitoring component substantially continuously transmits datato the processing component such that substantially real-time detectionof AF occurs.

If AF is detected, the system can be adapted to administer therapy torestore normal electrical activity to the heart. In some embodiments thetherapy is electrical pacing therapy administered by, for example,pacing electrodes disposed within the LAA and/or left atrium. Electricalimpulses can be delivered by electrodes that contact the cardiac muscleto pace the appendage or atrium for a short-term period of time totreat, for example, AF, atrial tachycardia, sick sinus rhythm, etc. Insome embodiments pacing occurs at regular intervals. For example, pacingcan occur for about 30 to about 90 seconds and occurs about every 6 toabout every 12 hours. These numerical ranges are merely exemplary.

In some embodiments the therapy comprises delivering a therapeutic agentinto the heart upon the detection of an arrhythmia. The implantablesystem can include a drug reservoir for delivery of one or moreanti-atrial fibrillation drugs if the patient goes into AF. In someembodiments the LAA occlusion device is placed near the ostium of theLAA, while the cardiac monitor and drug reservoir are disposed on theappendage side of the implant. The cardiac monitor is adapted to releasea prescribed amount of the therapeutic agent in the event AF is detectedand lasts longer than a prescribed period of time. The therapeutic agentadministered includes anti-arrhythmic and/or rate control and/oranticoagulation agents for AF. An example is Vernakalant, aninvestigational drug under regulatory review for the acute conversion ofAF. Exemplary rate control agents and doses include Metoprolol (e.g.,about 50 to about 100 mg), Atenolol (e.g., about 50 to about 100 mg),Propranolol (e.g., about 40 to about 80 mg), Acebutolol (e.g., about 200mg), Carvedilol (e.g., about 6.25 mg), Diltiazem (e.g., about 180 toabout 240 mg), Verapamil (e.g., about 180 to about 240 mg), and Digoxin(e.g., about 0.125 mg). Exemplary rhythm control agents and dosesinclude Propafenone (e.g., about 450 mg), Flecainide (e.g., about 200mg), Sotalol (e.g., about 240 mg), Dofetilide (e.g., about 500 mcg),Amiodarone (e.g., about 200 mg), Quinidine (e.g., about 600 to about 900mg). In some embodiments innovative anti-arrhythmic agents can be usedwith unconventional anti-arrhythmic mechanisms, such as stretch receptorantagonism, sodium-calcium exchanger blockade, late sodium channelinhibition, and gap junction modulation. These therapies have not yetreached clinical studies in AF but reports look promising.

In FIG. 1, anchoring element 16 can incorporate sensing elements such asring electrodes disposed on and around anchoring element 16. Anchoringelement 16 can also incorporate pacing, or stimulating, electrodesdisposed thereon. Any suitable anchoring element or anchoring structuredescribed herein can be adapted to include one or more electrodes formonitoring and/or pacing. For example, in FIG. 3, anchor 44 can beadapted to have one or more electrodes disposed thereon. The electrodeswould be adapted to be in contact with LAA tissue to monitor and/or pacethe tissue. Similarly, distal anchor 56 can also comprise electrodesdisposed thereon to monitor and/or pace LAA tissue.

In some embodiments, even if there is an anchoring structure within theLAA, an anchoring structure adjacent the LAA ostium can have electrodesdisposed thereon to monitor and/or pace tissue adjacent the ostium. Forexample, in the embodiment in FIG. 3, anchoring structure 46 can includeelectrodes disposed thereon. In FIG. 12, distal anchor can includemonitoring and/or pacing electrodes thereon. In some embodiments,connector 146 can be used as either the anode or the cathode and anelectrode within distal anchor 148 is the opposite of the electrode inconnector 146. Connector 146 is electrically coupled to the electrode indistal anchor 148.

FIGS. 14A-27 illustrate exemplary embodiments of how occluding devicesdescribed herein can be adapted to include monitoring and therapycomponents. For example, leaflets 202 in the embodiment in FIGS. 14A-Ccan be adapted to include sensing and/or pacing electrodes. When theleaflets are expanded in the left atrium, the distal sides of theleaflets engage atrial tissue. The leaflets, and optionally frame 101,can have electrodes disposed therein and can be in electrical connectionto hub 212 to other components that can provide power. Additionally, inthe embodiment in FIGS. 16A-16, hub 282 has a lumen therein that can beadapted to receive an elongate member that is to be disposed within theLAA. The elongate member can have one or more monitoring and/or pacingelectrodes thereon to be in contact with LAA tissue. In FIGS. 24A and24B, elongate element 410 can be the cathode or anode while electrode416 of bulb 406 is the opposite thereof. Electrode 416 is adapted to bein contact with LAA tissue and is adapted to monitor and/or pace thecardiac tissue.

While the implanted devices can be incorporated with sensing and/orstimulating functionality, the implanted devices, in some embodiments,include circuitry to process the monitored patient data and detect anarrhythmia. Processing the data can include known techniques, includingfiltering and amplifying a signal. Algorithms stored in the device candetermine if, based on the data, AF is occurring. Upon the detection ofan arrhythmia, the system can be adapted to automatically deliver atherapy, whether it is electrical pacing, drug delivery, or some othertype of therapy.

In some embodiments the processing and detecting steps occur in a deviceexternal to the heart, whether they are underneath the patient's skin orexternal to the patient. For example, an external device can be securedto the patient using a harness such that the device is securedcomfortably near the patient heart. The monitored data is transmitted tothe external device, which can include the processing and detectioncomponents. Once an arrhythmia is detected, the external device thencommunicates a signal to the internal device to initiate the therapy. Insome instances the data, raw or processed, is further transmitted to aremote location. For example, the data can be transmitted to a physicianfor review. In some instances the detection algorithm can bereprogrammed as needed, perhaps to provide better more accurate AFdetection.

The implanted device or any external device can include memory to storedata, either temporarily or permanently. The implanted device can storea certain amount of data, such as in a first-in-first-out process, or itcan transmit data to an external data, which then stores the data. Insome embodiments only data just before, during, and following AF isdesired. The system can be adapted to store in memory only data fromthat specific period of time. The stored data can additionally bereviewed by a health care provider as desired.

The implantable device can optionally include a power source, which isoptionally rechargeable (such as by inductive charging). The powersource can power the sensing and/or pacing electrodes, or any otherelectrically driven activities performed by the implant. The powersource is disposed in the implant and is in electrical communicationwith any monitoring and/or pacing electrodes.

The device can be adapted with additional sensors to acquire data tocalculate or determine any of the following: AF burden (i.e., the timethe patient is in AF as compared to sinus rhythm), left atrial pressure,temperature, transthoracic impedance (surrogate for pulmonary fluidstatus, i.e., “CHF”), impending atrial fibrillation or ventricularfibrillation. The implant can also include a pulse counter.

FIGS. 34A and 34B illustrate an alternative embodiment in which implant600 is adapted to occlude flow into the LAA, monitor patient data, anddispense a therapeutic agent into the LAA if an arrhythmia is detected.Implant 600 include expandable frame 606, which has a general mushroomconfiguration in an expanded configuration. The frame is secured tobarrier 604, which is adapted to prevent blood from entering the LAA.Barrier 604 only covers a proximal portion of frame 604, leaving adistal portion of frame 606 uncovered by the barrier. The open end ofthe frame faces into the LAA. The implant also includes delivery element602 that is adapted to be releasably coupled to a delivery tool (notshown). Implant 600 also includes cardiac monitor and therapeutic agentreservoir component 608. Component 608 is secured to the inside of theimplant 600. That is, component 608 is only exposed to the inside of theLAA and not the left atrium. The cardiac monitoring component iselectrically coupled to LAA tissue via leads 610 and monitors atrialactivity, such as electrograms. When the detection component (whether itis integrated with implant 600 or disposed external to the heart)detects an arrhythmia such as atrial fibrillation, component 608 can beprogrammed to automatically release a dose of an anti-atrialfibrillation therapeutic agent. The drug reservoir could be a reservoirwith a valve that when opened, releases the agent into the LAA. Thevalve, or any suitable actuatable element, can be electrically poweredby the power source within implant 600 to open to release the agent intothe LAA.

FIG. 35 illustrates an alternative embodiment of implant 700 that issimilar to implant 600 shown in FIGS. 34A and 34B. Implant 700 includesexpandable frame 702, barrier704, which is adapted to prevent blood fromentering the LAA. Barrier 704 only covers a proximal portion of frame702, leaving a distal portion of frame uncovered by the barrier. Theopen end of the frame faces into the LAA. The implant also includesdelivery element 708 that is adapted to be releasably coupled to adelivery tool (not shown). Implant 700 also includes cardiac monitor andtherapeutic agent reservoir component 706, which can provide the samefunctions as component 608 in the embodiment in FIGS. 34A and 34B.

FIGS. 37A-C illustrate an exemplary embodiment of a medical device in anexpanded, or deployed, configuration that is adapted to isolate materialin the left atrial appendage. Device 800 includes anchoring portion 802and barrier portion 804. Anchoring portion 802 includes four distalanchors 806 and four proximal anchors 810 (only two can be seen), all ofwhich are coupled to hub 808. Barrier portion 804 includes proximalbarrier 814 and distal barrier 812. Distal barrier 812 is secured todistal anchors 806, while proximal barrier 814 is secured to distalanchors 810. In this embodiment they are secured with sutures, as shown.

Each of the distal and proximal anchors has a looped configuration, thetwo ends of which are secured to hub. The loops are longer than they arewide. In their expanded configurations, the anchors 806 and 810 extendsubstantially radially outward from hub 808, and are generallyorthogonal to the longitudinal axis of hub 808. In other words, in theside view shown in FIG. 37B, the anchoring portion resembles the letter“H,” with the distal anchors 806 shorter than proximal anchors 810. Allof the distal anchors 806 are generally in the same plane, but areconstructed to be appropriately flexible to conform to the amorphousanatomy of the left atrial appendage, which is generally orthogonal tothe longitudinal axis of hub 808, which can be seen in the side view ofFIG. 37B. All of the proximal anchors are also generally in a singleplane, which is generally orthogonal to the longitudinal axis of hub808.

In this embodiment the anchoring portion, including the eight anchorsand the hub, is formed by laser cutting a single nitinol tube. Theanchors and hub need not be formed from the same starting material, andcan be secured to one another, such as by welding. The hub and theanchors need not be the same type of material. Materials other thannitinol can be used, and other cutting methods can be used.

In this embodiment, after the necessary material has been removed duringthe laser cutting process, the eight anchors are heat set in thedeployed configurations shown in FIGS. 37A-C, such that they aresubstantially orthogonal to hub 808. Barrier 814 and barrier 812 arethen secured to the anchors. In this embodiment they are sutured to theanchors, with the sutures as shown. Other methods of securing theanchors and barriers can be used. The proximal anchors 810 are securedto proximal barrier 814 such that proximal anchors 810 are on the distalside of proximal barrier 814. Distal anchors 806 are secured to distalbarrier 812 such that distal anchors 806 are disposed on the distal sideof distal barrier 812. For distal anchors 806 to be on the distal sideof distal barrier 812, there is a central hole in distal barrier 812.

The barriers can be a polyester material such as polyethyleneterephthalate (“PET”; trade name Dacron®). The barriers can be othersuitable materials, such as PTFE.

Proximal barrier 814 has pleats 816 formed therein between anchors 810.The pleats, or other rib formations, can help reduce the amount ofmaterial in the barrier, which can make it easier when the device isloaded into a delivery device. The pleats can help reduce the deliveryprofile of the device. The pleats or ribs also make it easier toaccommodate dimensional changes of the anchor elements with compressionon the barrier in the delivery configuration and tension on the barrierin the deployed configuration. Maintaining a low barrier thickness canalso ease the loading process and maintain a minimal delivery profile ofthe device. The barrier material can be selected to have a specificporosity. The device includes two barriers 814 and 812, whicheffectively creates a two-ply barrier, and thereby reduces the amount ofmaterial that can escape the left atrial appendage and into the leftatrium.

The barriers are adapted to prevent blood flow into the LAA, althoughthey could be adapted to filter blood such that they prevent clots fromflowing from the LAA into the left atrium. In alternative embodimentsthe device does not include distal barrier 812, such that the deviceonly includes a proximal barrier.

In an exemplary method of use, the device is used to occlude the leftatrial appendage such that material in the left atrial appendage cannotenter the left atrium. Device 800 is first loaded into a deliveryconfiguration in a delivery device, such as a catheter. Distal anchors806 are deformed by collapsing them toward the longitudinal axis of thehub, so that they extend generally distally from the hub and are movedcloser to one another. Proximal anchors 810 are also collapsed towardsthe longitudinal axis of the hub, moving them closer together such thatthey extend substantially proximally from the hub. The reconfigurationof proximal anchors 810 causes the barrier material 814 to bunch up,which is minimized by pleats, ribs, or other similar features. Pleats orribs can also be incorporated into the distal barrier 812. The devicecan be front-loaded into a distal end of the delivery device, such thatthe proximal anchors are deformed before the distal anchors.

In use, after the device has been advanced within the patient adjacentthe left atrial appendage (as described above), the distal anchors anddistal barrier are first deployed from the delivery device into the leftatrial appendage. Anchors 806 deform towards their deployedconfiguration shown in FIGS. 37A-C, such that they extend radially fromhub 808. As they deform, they will engage left atrial appendage tissue,anchoring the distal portion of the device in the left atrial appendage.Once the position of the anchors in confirmed using one or more imagingtechniques, the proximal anchors are then deployed from the deliverydevice such that the proximal anchors engage left atrial tissue andsecure the proximal barrier over the left atrial appendage ostium.Material in the left atrial appendage cannot escape the appendage andenter the atrium. The proximal anchors can have a deployed configurationin which they extend slightly distally relative to the hub, such thatthey apply a slight distally directed force on the atrial tissue, whichhelps anchor device in place relative to the atrial tissue. Similarly,the distal anchors can be biased to extend slightly in the proximaldirection relative to the hub to apply a slightly proximally directedforce on the left atrial appendage. In some embodiments the distalanchors and proximal anchors provide a slight or substantially clampingeffect on the tissue at the ostium, which helps secure the device inplace.

It should be noted that before the proximal anchors are deployed, if theposition of the deployed distal anchors is not optimal, the catheter canbe advanced distally, deforming the distal anchors forward towards theirdelivery configurations, while recapturing the distal anchors within thedelivery device.

Device 800 can similarly be adapted to include sensing and/or treatmentfeatures to sense and treat cardiac arrhythmias. For example, one ormore of the anchors 810 or 806 can have one or more electrodes disposedthereon adapted to delivery energy to cardiac tissue to pace the tissuein the event of a detected atrial fibrillation. Alternatively, hub 808can have a cylindrically shaped drug delivery device disposed therein,which is adapted to deliver a drug or other agent into the left atrialappendage, examples of which are disclosed above.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the disclosure. It should beunderstood that various alternatives to the embodiments of thedisclosure described herein may be employed in practicing thedisclosure.

What is claimed is:
 1. An implantable cardiac orifice occlusion devicepositioned within the left atrial appendage and/or left atrium,comprising: a first anchor positioned on a proximal side of the ostiumin the left atrium; a second anchor positioned on the distal side of theostium in the left atrial appendage, a ratcheting element coupled to thefirst and second anchors, the ratcheting element configured to adjustthe distance between the first and second anchors to securely clamptissue on opposite sides of the ostium; and; one or more barrierelements coupled to at least one anchor and adapted to seal the ostium.2. The device of claim 1, wherein the ratcheting element includes ashaft with teeth slidably coupled to the first anchor and fixedlycoupled to the second anchor, the ratcheting element being configured toretract proximally causing the teeth on the ratcheting element toratchet with respect to the first anchor while moving the first anchortoward the second anchor to clamp the tissue.
 3. The device of claim 2,wherein the teeth of the ratcheting element are configured to lock thefirst anchor on the shaft.
 4. The device of claim 1, wherein the firstand second anchors are generally annular shape.
 5. The implant of claim1, wherein the first and second anchors are self-expanding.
 6. Theimplant of claim 5, wherein the self-expanding first and second anchorsare configured to collapse or compress into a delivery configuration fordelivery of the implant to the LAA, and then self-expand after delivery.7. An implantable cardiac orifice occlusion device positioned within theleft atrial appendage and/or left atrium, comprising: a first anchor armhaving a first proximal portion positioned on the proximal side of theostium and a first distal portion positioned on the distal side of theostium; a second anchor arm having a second proximal portion positionedon the proximal side of the ostium opposite the first distal portion,and a second distal portion positioned on the distal side of the ostiumopposite the first proximal portion, a ratcheting element coupled to thefirst and second anchor arms, the ratcheting element configured torotate the first and second anchor arms between an open position and aclosed position to securely clamp tissue between the proximal portionsand the distal portions of the first and second anchor arms; one or morebarrier elements coupled to the first and second anchor arms and adaptedto occlude the flow of blood into the LAA when the first and secondanchor arms are in the closed position; and a distal appendage anchorcoupled to the first and/or second anchor arms by a connector, thedistal appendage anchor being configured to expand within the leftatrial appendage.
 8. The implant of claim 7, wherein the distalappendage anchor is self-expanding.
 9. The implant of claim 7, whereinthe self-expanding distal appendage anchor is configured to collapse orcompress into a delivery configuration for delivery to the LAA, and thenself-expand in the LAA after delivery.
 10. The device of claim 7,wherein the distal appendage anchor has a generally conical expandedconfiguration.
 11. The device of claim 7, wherein the distal appendageanchor is made from a single wire secured to the connector.
 12. Thedevice of claim 7, further comprising a delivery device coupled to theratcheting element configured to actuate the ratcheting element.
 13. Thedevice of claim 7, wherein the first and second anchor arms are adaptedwith a locking feature configured to lock the first and second anchorarms in a locked configuration.
 14. The device of claim 7, furthercomprising a cardiac monitoring element and/or treatment element securedto at least one anchor arm.
 15. The device of claim 14, wherein thecardiac monitoring element and/or treatment element are adapted towirelessly transmit and/or receive data with an external device.
 16. Aleft atrial appendage (LAA) occlusion implant, comprising: a proximalportion comprising multiple sized leaflets adapted to engage the atrialwall around the LAA and sized to not obstruct blood flow through themitral valve or the pulmonary vein, the multiple sized leaflets having:a frame element having a triangular or elliptical shape made from shapememory material with two ends coupled to a hub; a barrier covering theframe element, the barrier being adapted to prevent blood clots frompassing through the LAA; wherein the frame element includes an outerportion adapted to collapsed into a delivery configuration andself-expand when delivered; and a distal portion comprising a pluralityof anchors having a triangular or elliptical shape made of a shapememory material with two ends coupled to the hub, the plurality ofanchors having an outer portion adapted to collapse into a deliveryconfiguration and self-expand when delivered.
 17. The implant of claim16, wherein a central portion of each frame element is adapted to bendoutward to ease in the collapse of the frame element, and a centralportion of each anchor is adapted to bend outward to ease in thecollapse of the anchors.
 18. The implant of claim 16, wherein themultiple sized leaflets are adapted to overlap one another into astaggered orientation when collapsed.
 19. The implant of claim 16,wherein the multiple sized leaflets and anchors are adapted to bedelivered through a delivery instrument.
 20. A left atrial appendage(LAA) occlusion implant, comprising: a proximal portion comprisingmultiple sized leaflets adapted to engage the atrial wall around the LAAand sized to not obstruct blood flow through the mitral valve or thepulmonary vein, the multiple sized leaflets having: a frame elementhaving a triangular or elliptical shape with two ends coupled to atubular element; a barrier covering the frame element, the barrier beingadapted to prevent blood clots from passing through the LAA; and adistal portion comprising a plurality of struts extending from thetubular element and adapted to expand within the LAA to secure theimplant.
 21. The implant of claim 20, wherein the frame element is madeof a shape memory material adapted to collapse into a deliveryconfiguration and self-expand when delivered.
 22. The implant of claim20, wherein the struts are made of a shape memory material and adaptedto collapse into a delivery configuration and self-expand whendelivered.
 23. A left atrial appendage (LAA) occlusion implant,comprising: a proximal portion comprising multiple sized leafletsadapted to engage the atrial wall around the LAA and sized to notobstruct blood flow through the mitral valve or the pulmonary vein, themultiple sized leaflets having: a frame element having a triangular orelliptical shape with two ends coupled to a tubular hub; a barriercovering the frame element, the barrier being adapted to prevent bloodclots from passing through the LAA; and a distal portion comprising aplurality of anchors with two generally straight sections extending fromthe tubular hub with a curved section in between.
 24. The implant ofclaim 23, wherein the frame element is made of a shape memory materialadapted to collapse into a delivery configuration and self-expand whendelivered in the LAA.
 25. The implant of claim 23, wherein the anchorsare made of a shape memory material and adapted to collapse into adelivery configuration and self-expand when delivered.
 26. A left atrialappendage (LAA) occlusion implant, comprising: a proximal portioncomprising multiple sized leaflets having: a frame element with atriangular or elliptical shape with two ends coupled to a hub, themultiple sized leaflets being adapted to engage the atrial wall aroundthe LAA and sized to not obstruct blood flow through the mitral valve orthe pulmonary vein; a barrier covering the leaflets, the barrier beingadapted to prevent blood clots from passing through the LAA; a distalportion comprising a plurality of anchors with a triangular orelliptical shape with two ends coupled to the hub, the plurality ofanchors being adapted to expand in the LAA and anchor the implant inplace; and a distal expandable bulb anchor coupled to the hub by one ormore struts, the expandable bulb being adapted to inflate within the LAAto assist in anchoring the implant in place.
 27. The implant of claim26, wherein the distal expandable bulb is inflated with an inflationfluid.
 28. A left atrial appendage (LAA) occlusion implant, comprising:a barrier element adapted to prevent blood from entering the LAA; areinforcing frame coupled to the barrier element comprising a pluralityof reinforcing elements coupled to a hub; and a distal expandable bulbanchor coupled to the hub by one or more struts, the expandable bulbbeing adapted to inflate within the LAA to assist in anchoring theimplant in place.
 29. The implant of claim 26, wherein the one or morestruts comprise a coil spring that add flexibility to the implant. 30.The implant of claim 26, wherein the distal expandable bulb is inflatedwith an inflation fluid.
 31. A left atrial appendage (LAA) occlusionimplant, comprising: multiple proximal anchors coupled to a hub aproximal barrier element coupled to the proximal anchors, adapted toprevent blood from entering the LAA, the proximal barrier element havingpleats formed thereon between the proximal anchors; multiple distalanchors coupled to a hub; and a distal barrier element coupled to thedistal anchors, the distal barrier element having pleats formed thereonbetween the distal anchors;
 32. The implant of claim 31, wherein theproximal anchors are secured to the distal side of proximal barrier andthe distal anchors are secured to the distal side of distal barrier.